Novel anti-apoptotic microRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and Bim
| Autor: | Hannah Breit, Benjamin Kefas, Christel Herold-Mende, Anindya Dutta, Kaitlyn Marks, Roger Abounader, Michael Synowitz, Desiree Floyd, Rainer Glass, Ying Zhang, Bijan K. Dey, Benjamin Purow |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genetic Screens
medicine.medical_treatment Gene Identification and Analysis Cancer Treatment Gene Expression lcsh:Medicine medicine.disease_cause Stem cell marker Biochemistry RNA interference 0302 clinical medicine Cell Signaling Nucleic Acids Molecular Cell Biology Basic Cancer Research Medicine and Health Sciences AC133 Antigen lcsh:Science Neurological Tumors 3' Untranslated Regions Apoptotic Signaling Cascade Cells Cultured 0303 health sciences Multidisciplinary Cell Death Bcl-2-Like Protein 11 Caspase 3 Gene Therapy Glioma Stem-cell therapy Flow Cytometry Signaling Cascades Caspase 9 Neural stem cell 3. Good health Cell biology Gene Expression Regulation Neoplastic Neurology Oncology Cell Processes 030220 oncology & carcinogenesis Neoplastic Stem Cells Epigenetics Stem cell Research Article Signal Transduction Cell Survival Biology 03 medical and health sciences Antigens CD Cell Line Tumor Proto-Oncogene Proteins Precursor cell microRNA Genetics Cancer Genetics medicine Humans Molecular Biology Techniques Molecular Biology neoplasms Glycoproteins 030304 developmental biology Biology and life sciences lcsh:R Cancers and Neoplasms Membrane Proteins Human Genetics Cell Biology RNA stability MicroRNAs RNA processing RNA Protein Translation lcsh:Q Apoptosis Regulatory Proteins Glioblastoma Peptides Carcinogenesis Glioblastoma Multiforme |
| Zdroj: | PLoS ONE, Vol 9, Iss 5, p e96239 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Glioblastoma is the most common and lethal primary brain tumor. Tumor initiation and recurrence are likely caused by a sub-population of glioblastoma stem cells, which may derive from mutated neural stem and precursor cells. Since CD133 is a stem cell marker for both normal brain and glioblastoma, and to better understand glioblastoma formation and recurrence, we looked for dys-regulated microRNAs in human CD133+ glioblastoma stem cells as opposed to CD133+ neural stem cells isolated from normal human brain. Using FACS sorting of low-passage cell samples followed by microRNA microarray analysis, we found 43 microRNAs that were dys-regulated in common in three separate CD133+ human glioblastomas compared to CD133+ normal neural stem cells. Among these were several microRNAs not previously associated with cancer. We then verified the microRNAs dys-regulated in glioblastoma using quantitative real time PCR and Taqman analysis of the original samples, as well as human GBM stem cell and established cell lines and many human specimens. We show that two candidate oncogenic microRNAs, miR-363 and miR-582-5p, can positively influence glioblastoma survival, as shown by forced expression of the microRNAs and their inhibitors followed by cell number assay, Caspase 3/7 assay, Annexin V apoptosis/fluorescence activated cell sorting, siRNA rescue of microRNA inhibitor treatment, as well as 3'UTR mutagenesis to show luciferase reporter rescue of the most successful targets. miR-582-5p and miR-363 are shown to directly target Caspase 3, Caspase 9, and Bim. |
| Databáze: | OpenAIRE |
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